Ribozyme和DNAzyme的基因治疗实验应用进展

Ribozyme和DNAzyme具有水解mRNA分子的功能,是阻断基因表达和抗病毒的重要工具。近年来,Ribozyme和DNAzyme在临床治疗研究中已经获得了长足进展,有许多成功的实例。比较了Ribozyme和DNAzyme的差异和特点,总结了它们在抗病毒、抗肿瘤、治疗遗传病、治疗神经系统疾病等方面的临床前研究、应用及进展。     

植物几丁质酶的结构与功能、分类及进化

近年来对几丁质酶的研究越来越深入,资料也愈来愈多,有的植物几丁质酶除具有几丁质酶活性,还具有其它的活性,典型的几丁质酶由－N－端信号区,催化区和C－端延伸区组成,有的还有几丁质结合域,各项能域具有各自的功能,对植物几丁质酶的分类已经过多次改进,目前公认的分成4组9个亚组,有证据表明植物几丁质酶在进化过程中有遗传转座现象,但具有进化过程还有待进一步确证,对几丁质酶与其它一些蛋白的关系的了解有助于理解几丁质酶的起源和进化,由于几丁质酶具有独特的抗真菌特性,因而几丁质酶基因成为目前抗真菌基因工程研究的热之一。     

Poloxamers and poloxamines in nanoparticle engineering and experimental medicine

Poloxamers and poloxamine nonionic surfactants have diverse applications in various biomedical fields ranging from drug delivery and medical imaging to management of vascular diseases and disorders. Although this is a progressive, rapidly advancing field in biotechnology, the future will depend on the recognition and rectification of a range of toxicity issues, which have to be addressed but have frequently been ignored until now.     

植物几丁质酶的结构与功能、分类及进化

近年来对几丁质酶的研究越来越深入,资料也愈来愈多。有的植物几丁质酶除具有几丁质酶活性,还具有其它的活性。典型的几丁质酶由N_端信号区、催化区和C_端延伸区组成,有的还有几丁质结合域。各功能域具有各自的功能。对植物几丁质酶的分类已经过多次改进,目前公认的是分成4组9个亚组。有证据表明植物几丁质酶在进化过程中有遗传转座现象,但具体进化过程还有待进一步确证。对几丁质酶与其它一些蛋白的关系的了解有助于理解几丁质酶的起源和进化。由于几丁质酶具有独特的抗真菌特性,因而几丁质酶基因成为目前抗真菌基因工程研究的热点之一。     

Chemistry and biology of arabinofuranosyl- and galactofuranosyl-containing polysaccharides

Polysaccharides containing galactofuranosyl and arabinofuranosyl residues are key components of many microorganisms. Recent investigations have provided a greater understanding of the biosynthetic pathways by which these glycans are assembled. Concomitant with these biochemical studies, an increasing number of chemical syntheses of oligofuranosides have been reported and new methods for their assembly have been developed.     

miRNA与涡虫再生

miRNA是一类具有调节功能的非编码小分子RNA,参与调节多种细胞功能。涡虫具有强大的再生能力,逐渐成为干细胞功能和再生研究的良好的动物模型。本文对miRNA在动物再生中的功能,尤其是miRNA与涡虫再生的关系进行综述。     

Ribonucleases and angiogenins from fish

For the first time fish RNases have been isolated and characterized. Their functional and structural properties indicate that they belong to the RNase A superfamily (or tetrapod RNase superfamily), now more appropriately described as the vertebrate RNase superfamily. Our findings suggest why previously repeated efforts to isolate RNases from fish tissues have met with no success; fish RNases have a very low ribonucleolytic activity, and their genes have a low sequence identity with those of mammalian RNases. The investigated RNases are from the bony fish Danio rerio (or zebrafish). Their cDNAs have been cloned and expressed, and the three recombinant proteins have been purified to homogeneity. Their characterization has revealed that they have indeed a very low RNA-degrading activity, when compared with that of RNase A, the superfamily prototype, but comparable with that of mammalian angiogenins; that two of them have angiogenic activity that is inhibited by the cytosolic RNase inhibitor. These data and a phylogenetic analysis indicate that angiogenic fish RNases are the earliest diverging members of the vertebrate superfamily, suggesting that ribonucleases with angiogenic activity were the ancestors of all ribonucleases in the superfamily. They later evolved into both mammalian angiogenins and, through a successful phylogenesis, RNases endowed with digestive features or with diverse bioactivities.     

The Opisthokonta and the Ecdysozoa may not be clades: stronger support for the grouping of plant and animal than for animal and fungi and stronger support for the Coelomata than Ecdysozoa

In considering the best possible solutions for answering phylogenetic questions from genomic sequences, we have chosen a strategy that we suggest is superior to others that have gone previously. We have ignored multigene families and instead have used single-gene families. This minimizes the inadvertent analysis of paralogs. We have employed strict data controls and have reasoned that if a protein is not capable of recovering the uncontroversial parts of a phylogenetic tree, then why should we use it for the more controversial parts? We have sliced and diced the data in as many ways as possible in order to uncover the signals in that data. Using this strategy, we have tested two controversial hypotheses concerning eukaryotic phylogenetic relationships: the placement of arthropoda and nematodes and the relationships of animals, plants, and fungi. We have constructed phylogenetic trees from 780 single-gene families from 10 completed genomes and amalgamated these into a single supertree. We have also carried out a total evidence analysis on the only universally distributed protein families that can accurately reconstruct the uncontroversial parts of the phylogenetic tree: a total of five families. In doing so, we ignore the majority of single-gene families that are universally distributed as they do not have the appropriate signals to recover the uncontroversial parts of the tree. We have also ignored every protein that has ever been used previously to address this issue, simply because none of them meet our strict criteria. Using these data controls, site stripping, and multiple analyses, 24 out of 26 analyses strongly support the grouping of vertebrates with arthropods (Coelomata hypothesis) and plants with animals. In the other two analyses, the data were ambivalent. The latter finding overturns an 11-year theory of Eukaryotic evolution; the first confirms what has already been said by others. In the light of this new tree, we re-analyze the evolution of intron gain and loss in the rpL14 gene and find that it is much more compatible with the hypothesis presented here than with the Opisthokonta hypothesis.     

Pseudocholinesterase activity and E1 phenotypes in Down's syndrome and mental retardation.

Pseudocholinesterase activity and the phenotypes controlled by the E1 locus have been determined in a sample of 307 Down's syndrome patients and 206 patients suffering from nonspecific mental retardation and compared to those in the healthy population. Both groups of patients have an elevated frequency of phenotypes possessing the rate E1f allele. The mentally retarded patients have a higher mean pseudocholinesterase activity than those with Down's syndrome who, in turn, have activity than the healthy controls.     

Duration between marriage and first birth and marital instability

This paper considers whether marital instability varies by the duration between marriage and 1st birth among ever-married white and black American women. Analysis of data from the June 1985 Current Population Survey suggests that the duration between marriage and 1st birth has a generally monotonic relationship with the probability of white women separating or divorcing from their 1st marriage; the relationship has remained relatively constant over time. For blacks, no consistent association is found between marital dissolution and the duration between marriage and 1st birth. Black women having a premarital conception and postmarital birth and those having their 1st birth during their 2nd year of marriage have a similarly high risk of dissolution. Conversely, blacks having their 1st birth 8-12 or 25-42 months after marrying have a low probability of dissolution. Childless women and those with premarital births generally has the greatest probability of marital disruption for whites. Racial differences may occur because blacks view the 1st birth and marriage differently than whites. That is, because blacks are much more likely to have premarital births and to have a shorter duration between marriage and 1st birth, blacks and whites in the same 1st birth interval category may be dissimilar and have different values resulting in a differential effect of the timing of the 1st birth on marital instability by race. Caution is needed when interpreting the pattern of association between delayed childbearing (and to a lesser extent, births occuring a few years after marriage) and marital instability. Results for whites were similar at each marriage duration and it is assumed delayed childbearing was not a result of marital instability. Marital instability was expected to have its strongest effect on the timing of the 1st birth during the 1st years of marriage. Marital instability may be partially responsible for the delaying of childbearing among blacks. However, blacks who delay but are married at 1st birth have a relatively low risk of separating or divorcing.     

Lipids of Salmonella typhimurium and Escherichia coli: structure and metabolism

The nature and quantity of the phospholipids of Salmonella typhimurium and Escherichia coli K-12 have been examined. The main classes of phospholipids, phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin have been completely characterized. Four minor compounds have been detected: phosphatidylserine, phosphatidic acid, and two partially characterized lipids. The phospholipid composition of the two organisms is quite similar, the only difference is the absence of one of the minor components and a decreased level of all components in E. coli. A study of the turnover of the phosphate in the phospholipids demonstrated no turnover in phosphatidylethanolamine, a slow turnover in phosphatidylglycerol, and a slow turnover in cardiolipin with, possibly, a transfer of phosphate from phosphatidylglycerol to cardiolipin. The amino acid phenylalanine is shown to become incorporated intact into lipidic compounds which have been partially characterized. Methods for the isolation and separation of lipids have been examined for their utility with these bacteria.     

Structure and Secretion of the Graptolite Prosicula, and its Application for Biostratigraphical and Evolutionary Studies

Studies on graptolite taxonomy and phylogeny in recent years have placed great emphasis on the proximal development of the rhabdosome, particularly the presence or absence of a virgella and early thecal growth patterns. As the prosicula was the earliest part of the graptolite skeleton to be secreted, it may also reveal fundamental information about evolutionary relationships within the Graptoloidea. The prosiculae from a variety of Ordovician taxa ranging in age from Tremadoc to Caradoc have been examined using a combination of light microscopy, SEM and TEM. Parameters investigated include the overall morphology, transition into the nema, pattern of longitudinal ridges and spiral line. Taxa show a change from early Tremadoc graptoloids which have a low diaphragm, prominent spiral line and lack longitudinal ridges, through late Tremadoc and early Arenig taxa which have longitudinal cortical bandages or spiralled, paired longitudinal ridges, into later Arenig and Llanvirn forms which have simple longitudinal ridges and indistinct spiral line and diaphragm. With additional work at higher stratigraphical levels, graptolite prosiculae may prove to be useful biostratigraphically when more complete material is absent, such as in palynomorph preparations from subsurface studies.     

Structure and biology of cartilage and bone matrix noncollagenous macromolecules

Over recent years a number of cartilage and bone matrix molecules have been identified and characterized. These include major constituents such as collagens and proteoglycans as well as a number of less-abundant matrix proteins. In several cases these proteins have been characterized by cloning and sequence analysis of the corresponding cDNA. Some properties of the macromolecules have been studied and an understanding of their functions in the structure, assembly, and breakdown of connective tissue matrix is emerging. It appears that some of these molecules have structural roles whereas others participate in the assembly of the tissue. In this paper we attempt to give a current picture of the organization and role of the noncollagenous matrix macromolecules in cartilage and bone.     

Opiate tolerance and dependence: recent findings and synthesis.

Recent studies have led to a greater understanding of the behavioral, cellular, and molecular mechanisms underlying opiate tolerance and physical dependence. Behavioral studies have demonstrated that both direct pharmacological effects and the learning of interactions between drug effects and environmental cues are important in these phenomena. Behavioral studies have also revealed that N-methyl-D-aspartate receptors may play a role in their development (or acquisition). Although in early cellular studies no consistent role was found for opioid receptors or endogenous opioid peptides in opiate tolerance and dependence, recent experiments suggest that beta-endorphin, enkephalin, and dynorphin neurons may indeed have a role. Finally, studies at the molecular level suggest that a functional decoupling of opioid receptors from GTP-binding proteins (G proteins) may be important. In this review, we discuss these disparate findings and present a synthesis that shows how they might together contribute to the phenomena of opiate tolerance and physical dependence.     

Protein arrays and microarrays

In the past, studies of protein activities have focused on studying a single protein at a time, which is often time-consuming and expensive. Recently, with the sequencing of entire genomes, large-scale proteome analysis has begun. Arrays of proteins have been used for the determination of subcellular localization, analysis of protein-protein interactions and biochemical analysis of protein function. New protein-microarray technologies have been introduced that enable the high-throughput analysis of protein activities. These have the potential to revolutionize the analysis of entire proteomes.     

Chance and the origin of life

Random chemical reactions in the Earth's primitive hydrosphere could have generated no more than 200 bits of information, whereas the first Darwinian organism must have encoded about a million bits, and therefore could not have arisen by chance. This information gap is bridged by separating reproduction from organism, and postulating a reproductive chemical community that would generate information by proto-Darwinian evolution. The information content of the initial community could have been as low as 160 bits, and its evolution might have led to the first Darwinian cell.     

Topological and phylogenetic analyses of bacterial holin families and superfamilies

Holins are small “hole-forming” transmembrane proteins that mediate bacterial cell lysis during programmed cell death or following phage infection. We have identified fifty two families of established or putative holins and have included representative members of these proteins in the Transporter Classification Database (TCDB; www.tcdb.org). We have identified the organismal sources of members of these families, calculated their average protein sizes, estimated their topologies and determined their relative family sizes. Topological analyses suggest that these proteins can have 1, 2, 3 or 4 transmembrane α-helical segments (TMSs), and members of a single family are frequently, but not always, of a single topology. In one case, proteins of a family proved to have either 2 or 4 TMSs, and the latter arose by intragenic duplication of a primordial 2 TMS protein-encoding gene resembling the former. Using established statistical approaches, some of these families have been shown to be related by common descent. Seven superfamilies, including 21 of the 52 recognized families were identified. Conserved motif and Pfam analyses confirmed most superfamily assignments. These results serve to expand upon the scope of channel-forming bacterial holins.     

Design and synthesis of mono- and multimeric targeted radiopharmaceuticals based on novel cyclen ligands coupled to anti-MUC1 aptamers for the diagnostic imaging and targeted radiotherapy of cancer

Targeted radiopharmaceuticals offer the possibility of improved tumor imaging and radiotherapy, with reduced side effects. A variety of monoclonal antibodies and antibody fragments have previously been successfully radiolabeled and used in diagnostic imaging and targeted radiotherapy of cancer. Many such antibodies have been shown to recognize the well-characterized MUC1 tumor marker and have recently been in clinical trials. Furthermore, a number of chelators have been synthesized and are currently used as radiopharmaceuticals for imaging and therapy. We now report the synthesis of a novel, cyclen-based ligand with a sulfur-containing arm that offers increased stability of the ligand-metal complex. We have coupled this ligand with previously selected aptamers to the MUC1 tumor marker to generate a novel targeted radiopharmaceutical with improved properties. We have tested the complex against known, commercially available chelators such as MAG3 in model breast cancer systems. To improve the pharmacokinetic properties of the aptamer-based targeted radiopharmaceutical, we have generated multi-aptamer complexes around a central chelator. Such multi-aptamer complexes have increased retention of the complex in circulation, without affecting the lack of immunogenicity of the complex or altering its superior tumor penetration properties.     

Clinical aspects of gastric cancer and Helicobacter pylori--screening, prevention, and treatment

Gastric cancer still represents a global health care burden, and in the absence of strategies implemented for early detection, the disease continues to have a dismal prognosis. Patients presenting with clinical manifestations of gastric cancer have limited options for cure. Thus, early detection and prevention play a key role in the fight against gastric cancer. Serologic-based test methods have the potential to detect a subset of patients at high risk of gastric cancer that require a close clinical and endoscopic follow-up. More data have been produced to support Helicobacter pylori eradication as an efficient strategy to prevent gastric cancer. Treatment options for patients with an advanced disease are still limited, but the introduction of new agents opens a more optimistic perspective for the future.     

HIV Infection and Sexual Risk among Men Who Have Sex with Men and Women (MSMW): A Systematic Review and Meta-Analysis

Objectives

To estimate the number of men who have sex with men and women who are HIV-positive in the United States, and to compare HIV prevalence rates between men who have sex with men and women, men who have sex with men only, and men who have sex with women exclusively.

Methods

Following PRISMA guidelines, we conducted a systematic review and meta-analysis of reports referencing HIV prevalence and men who have sex with men and women. We searched PubMed and Ovid PsycINFO for peer-reviewed, U.S.-based articles reporting on HIV prevalence among men who have sex with men and women. We conducted event rate, effect size, moderation and sensitivity analyses.

Results

We estimate that 1.0% of U.S. males are bisexually-behaving, and that 121,800 bisexually-behaving men are HIV-positive. Men who have sex with men and women are less than half as likely to be HIV-positive as men who have sex with men only (16.9% vs. 33.3%; OR = 0.41, 95% CI: 0.31, 0.54), but more than five times as likely to be HIV-positive as men who have sex with women exclusively (18.3% vs. 3.5%; OR = 5.71, 95% CI: 3.47, 9.39). They are less likely to engage in unprotected receptive anal intercourse than men who have sex with men only (15.9% vs. 35.0%; OR = 0.36, 95% CI: 0.28, 0.46). Men who have sex with men and women in samples with high racial/ethnic minority proportions had significantly higher HIV prevalence than their counterparts in low racial/ethnic minority samples.

Conclusions

This represents the first meta-analysis of HIV prevalence in the U.S. between men who have sex with men and women and men who have sex with men only. Data collection, research, and HIV prevention and care delivery specifically tailored to men who have sex with men and women are necessary to better quantify and ameliorate this population’s HIV burden.